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Published on: February 16, 2015
Engulfed cell remnants, and not cells undergoing apoptosis, constitute the LE-cell phenomenon
Eva Feierl1, Josef S Smolen, Thomas Karonitsch
1Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria.
Insights
Systemic lupus erythematosus LE cells form when autoantibodies bind necrotic cell remnants, not early apoptotic cells. This finding clarifies the nature of material engulfed during LE cell formation.
Area of Science:
- Immunology
- Cell Biology
- Rheumatology
Background:
- LE cells are a key diagnostic marker for active systemic lupus erythematosus (SLE).
- LE cell formation involves phagocytes engulfing cellular material of debated origin.
- Autoantibodies targeting linker histone H1 are crucial for LE cell formation.
Purpose of the Study:
- To investigate the specific cellular material bound by anti-histone H1 antibodies and LE cell-positive sera.
- To differentiate between early apoptotic and necrotic cells in the context of LE cell formation.
Main Methods:
- Induction of apoptosis in cells using gliotoxin or actinomycin D.
- Induction of necrosis in cells via heating.
- Assessment of binding by anti-histone H1 antibodies and LE cell-positive sera to treated cells.
Main Results:
- Anti-histone H1 antibodies and LE cell-positive sera bound to necrotic cell remnants.
- These antibodies and sera did not bind to early apoptotic cells.
- LE cell formation involves the engulfment of necrotic or late apoptotic material.
Conclusions:
- LE cell formation is dependent on anti-histone H1 autoantibodies.
- The process specifically targets necrotic (or late apoptotic) cellular material, not early apoptotic cells.
- This clarifies the immunological basis of LE cell diagnostics in SLE.
Abstract:
The LE cell has been one of the first immunological signs of active systemic lupus erythematosus, included into the ACR criteria. LE cells consist of a phagocyte engulfing material of disputed origin, which was interpreted as either cellular remnants from necrotic cells or as early apoptotic cells. It is well established that LE cell formation is dependent on autoantibodies against the linker histone H1. In view of this fact, we investigated whether anti-histone H1 antibodies and LE cell positive sera bound to cells where apoptosis had been induced by gliotoxin or actinomycin D or which were necrotic after heating. Necrotic cell remnants, but not (early) apoptotic cells were bound by anti-histone H1 antibodies and LE cell positive sera, establishing that the process of LE cell formation, which is dependent on anti-H1 binding, leads to engulfment of necrotic (or late apoptotic) material, but not of early apoptotic cells.
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